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      Comparison of Two Rodent Models of Maternal Separation on Juvenile Social Behavior

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          Abstract

          Early childhood deprivation is associated with an increased risk of attachment disorders and psychopathology. The neural consequences of exposure to stress early in life have used two major rodent models to provide important tools for translational research. Although both models have been termed maternal separation (MS), the paradigms differ in ways that clearly shift the focus of stress between maternal and offspring units. The first model, here called early deprivation (ED), isolates pups individually while the dam is left not alone, but with a subset of littermates in the home nest (“stay-at-homes”). The other model, here called MS, isolates the dam in a novel cage while the pups are separated together. In this study, these two early stress models were directly compared for their effects on social behaviors in male and female juvenile offspring. Although both models altered play behavior compared to controls, patterns of prosocial behaviors versus submissive behaviors differed by model and sex. Additionally, there were main effects of sex, with female ED subjects exhibited masculinizing effects of early stress during play sessions. Maternal behavior upon reunion with the isolated subjects was significantly increased in the MS condition compared to both ED and control conditions, which also differed but by a lesser magnitude. “stay-at-homes” were tested since some laboratories use them for controls rather than undisturbed litters; they displayed significantly different sex-dependent play compared to undisturbed subjects. These results indicate that early stress effects vary by paradigm of separation. We suggest that MS produces greater stress on the dam and thus greater maternal mediation, while ED causes greater stress on the neonates, resulting in different behavioral sequela that warrant attention when using these models for translational research.

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          Most cited references36

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          Maternal care, hippocampal glucocorticoid receptors, and hypothalamic-pituitary-adrenal responses to stress.

          Variations in maternal care affect the development of individual differences in neuroendocrine responses to stress in rats. As adults, the offspring of mothers that exhibited more licking and grooming of pups during the first 10 days of life showed reduced plasma adrenocorticotropic hormone and corticosterone responses to acute stress, increased hippocampal glucocorticoid receptor messenger RNA expression, enhanced glucocorticoid feedback sensitivity, and decreased levels of hypothalamic corticotropin-releasing hormone messenger RNA. Each measure was significantly correlated with the frequency of maternal licking and grooming (all r's > -0.6). These findings suggest that maternal behavior serves to "program" hypothalamic-pituitary-adrenal responses to stress in the offspring.
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            Maternal care, hippocampal synaptogenesis and cognitive development in rats.

            We report that variations in maternal care in the rat promote hippocampal synaptogenesis and spatial learning and memory through systems known to mediate experience-dependent neural development. Thus, the offspring of mothers that show high levels of pup licking and grooming and arched-back nursing showed increased expression of NMDA receptor subunit and brain-derived neurotrophic factor (BDNF) mRNA, increased cholinergic innervation of the hippocampus and enhanced spatial learning and memory. A cross-fostering study provided evidence for a direct relationship between maternal behavior and hippocampal development, although not all neonates were equally sensitive to variations in maternal care.
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              Maternal separation enhances offensive play-fighting, basal corticosterone and hypothalamic vasopressin mRNA expression in juvenile male rats.

              Early life stress is a risk factor for altered adult emotionality including impaired social behavior, enhanced aggression and violence. These behavioral deficits most likely have an earlier onset in life. We recently demonstrated that maternal separation (MS, 3h daily on postnatal day 1-14) increased intermale aggression in adult Wistar rats. Here, we investigated whether MS induced alterations in juvenile play-fighting, which is a precursor of aggression. MS increased offensive play-fighting behaviors in juvenile male rats, as indicated by a twofold increase in the number of nape attacks, a higher frequency of offensive pulling and biting, and a lower frequency of submissive play behaviors. Furthermore, MS rats showed higher plasma corticosterone levels and higher vasopressin mRNA expression in the paraventricular nucleus and the bed nucleus of the stria terminalis compared with control rats during the early dark phase. Thus, MS enhanced aggressive play-fighting accompanied by changes in several relevant neuroendocrine parameters. Taken together with previous findings, the increase in aggressive behaviors both at juvenile and adult age illustrates that exposure to MS alters the way rats cope with social conflict situations throughout life.
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                Author and article information

                Journal
                Front Psychiatry
                Front. Psychiatry
                Frontiers in Psychiatry
                Frontiers Research Foundation
                1664-0640
                28 June 2011
                2011
                : 2
                : 39
                Affiliations
                [1] 1simpleDepartment of Psychology, Williams College Williamstown, MA, USA
                Author notes

                Edited by: Josephine Johns, University of North Carolina at Chapel Hill, USA

                Reviewed by: Elizabeth McCone Byrnes, Tufts University Cummings School of Veterinary Medicine, USA; Kelly Lambert, Randolph-Macon College, USA

                *Correspondence: Betty Zimmerberg, Department of Psychology, Williams College, 18 Hoxsey Street, Williamstown, MA 01267, USA. e-mail: betty.zimmerberg@ 123456williams.edu

                This article was submitted to Frontiers in Child and Neurodevelopmental Psychiatry, a aspecialty of Frontiers in Psychiatry.

                Article
                10.3389/fpsyt.2011.00039
                3128242
                21747771
                4e71352e-e524-4ed7-b606-3b5bf7477537
                Copyright © 2011 Zimmerberg and Sageser.

                This is an open-access article subject to a non-exclusive license between the authors and Frontiers Media SA, which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and other Frontiers conditions are complied with.

                History
                : 24 March 2011
                : 14 June 2011
                Page count
                Figures: 3, Tables: 2, Equations: 0, References: 40, Pages: 10, Words: 7862
                Categories
                Psychiatry
                Original Research

                Clinical Psychology & Psychiatry
                social behavior,maternal behavior,maternal separation,neonatal isolation,play behavior,early deprivation,stress,isolation

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